4Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo/JP

5Hospital Director, Tokai Central Hospital, Kakamigahara/JP

Abstract

Background

In Japan, oxaliplatin/5-FU/leucovorin (mFOLFOX6) is the most frequent first-line chemotherapy for metastatic colorectal cancer (mCRC). However, peripheral nerve disorders due to oxaliplatin (OXA) may decrease quality of life. For patients who discontinue OXA with no peripheral nerve disorders, OXA re-introduction at a later stage may be possible. This “stop and go” OXA approach with 5-FU/leucovorin maintenance was explored in the OPTIMOX-1 study and showed efficacy similar to continuous OXA administration. This study evaluates the safety and efficacy of mFOLFOX6 plus panitumumab induction with 5-FU/leucovorin + panitumumab maintenance in first-line mCRC patients.

Trial design

This phase II, multi-center, open-label, randomized, controlled study was designed to evaluate efficacy and safety in patients with chemotherapy-naÃ¯ve, KRAS wild-type mCRC after 6 cycles of mFOLFOX6 + panitumumab and subsequently assigning them to continuing mFOLFOX6 + panitumumab (Group A) or 5-FU/LV + panitumumab (Group B). Eligible patients will be treated with 6 cycles of mFOLFOX6 + panitumumab. Patients with ECOG performance status (PS) of 0-1 before the 7th cycle and no progressive disease (PD) using the Response Evaluation Criteria in Solid Tumors (RECIST) on imaging after the 6th cycle will be randomized to either group at a ratio of 1:1. After randomization, Group A or Group B treatment will be continued until the criteria for discontinuation of treatment due to toxicity or lack of efficacy (PD) are met. The primary efficacy endpoint is progression-free survival (PFS) 9 months after randomization. Secondary endpoints include PFS, overall survival, response rate, and time to treatment failure. Safety will be evaluated based on incidence of adverse events, including peripheral nerve disorders and skin disorders, and their severity. Enrollment began in September 2014, and 100 patients after randomization will be recruited; 55 subjects have been enrolled as of July 31, 2015. The final analysis will be performed when the last patient enrolled has been followed-up for 20 months.

Clinical trial identification

NCT02337946

Disclosure

N. Nagata, J. Sakamoto: consultation fees from Takeda Pharmaceutical Company Limited. H. Mishima: research support and honoraria from Takeda Pharmaceutical Company Limited. S. Kurosawa: employee of Takeda Pharmaceutical Company Limited. All other authors have declared no conflicts of interest.